Relationship between adherence to hepatitis C virus therapy and virologic outcomes: a cohort study

Abstract

Background: Adherence to therapy with pegylated interferon and ribavirin for hepatitis C virus (HCV) infection has been incompletely examined.

Objective: To evaluate the relationship between adherence to HCV therapy and early and sustained virologic response, assess changes in adherence over time, and examine risk factors for nonadherence.

Design: Retrospective cohort study.

Setting: National Veterans Affairs Hepatitis C Clinical Case Registry.

Patients: 5706 HCV-infected patients (genotypes 1, 2, 3, or 4) with at least 1 prescription for both pegylated interferon and ribavirin between 2003 and 2006 and HCV RNA results before and after treatment initiation.

Measurements: Adherence was calculated over 12-week intervals by using pharmacy refill data. End points included early virologic response (decrease of ≥2 log(10) HCV RNA at 12 weeks) and sustained virologic response (undetectable HCV RNA 24 weeks after the end of treatment).

Results: Early virologic response increased with higher levels of adherence to ribavirin therapy over the initial 12 weeks (patients with HCV genotype 1 or 4, 25 of 68 [37%] with ≤40% adherence vs. 1367 of 2187 [63%] with 91% to 100% adherence [P < 0.001]; patients with HCV genotype 2 or 3, 12 of 18 [67%] with ≤40% adherence vs. 651 of 713 [91%] with 91% to 100% adherence [P < 0.001]). Among patients with HCV genotype 1 or 4, sustained response increased with higher adherence to ribavirin therapy over the second, third, and fourth 12-week intervals. Results were similar for adherence to interferon therapy. Mean adherence to therapy with interferon and ribavirin decreased by 3.4 and 6.6 percentage points per 12-week interval, respectively (P for trend < 0.001 for each drug). Patients who received growth factors or thyroid medications during treatment had higher mean adherence to antiviral therapy.

Limitation: This was an observational study without standardized timing for outcome measurements.

Conclusion: Early and sustained virologic responses increased with higher levels of adherence to interferon and ribavirin therapy. Adherence to therapy with both antivirals decreased over time, but more so for ribavirin.

Figure 1

Selection of chronic hepatitis C virus-infected patients for inclusion in the study.

Figure 2

Proportion of patients with early virologic response at each level of adherence to pegylated interferon and ribavirin over the initial 12 weeks of therapy, by hepatitis C genotype.

Figure 3

Proportion of patients with sustained virologic response at each level of adherence to pegylated interferon and ribavirin over latter 12-week adherence intervals for hepatitis C genotypes 1 / 4 and genotypes 2 / 3.